Extracellular vesicles from mesenchymal stromal cells primed with synthetic toll-like receptor 4 agonists treat hematopoietic acute radiation syndrome.

ABSTRACT: Whole-body exposure to ionizing radiation can lead to cellular DNA damage to bone marrow (BM), causing lethal hematopoietic acute radiation syndrome (H-ARS). Extracellular vesicles (EVs) from human BM-derived mesenchymal stromal cells were primed with CRX-527 (CRX), a synthetic TLR4 agonist, characterized and tested as a radiomitigator therapy. Using a xenogeneic H-ARS mouse model, a single in vivo treatment with CRX-EVs administered 4 or 24 hours after lethal irradiation significantly improved weight loss, clinical scores and prolonged survival compared to control treatments. Ex vivo generation of CRX-EV educated monocytes (CRX-EEMos) were also effective in a H-ARS model when administered 24 hours after lethal irradiation. CRX-EVs or CRX-EEMos significantly promoted hematopoiesis in BM an

SUBMITTER: Kink JA 

PROVIDER: S-EPMC12784198 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature